Effect of fetal hemoglobin on microvascular regulation in sickle transgenic-knockout mice

In sickle cell disease, intravascular sickling and attendant flow abnormalities underlie the chronic inflammation and vascular endothelial abnormalities. However, the relationship between sickling and vascular tone is not well understood. We hypothesized that sickling-induced vaso-occlusive events a...

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Veröffentlicht in:	The Journal of clinical investigation 2004-10, Vol.114 (8), p.1136-1145
Hauptverfasser:	Kaul, Dhananjay K, Liu, Xiao-du, Chang, Hee-Yoon, Nagel, Ronald L, Fabry, Mary E
Format:	Artikel
Sprache:	eng
Schlagworte:	Acetylcholine - pharmacology Anemia Anemia, Sickle Cell - genetics Anemia, Sickle Cell - metabolism Animals Bioavailability Biomedical research Blood Cell Adhesion - physiology Cyclooxygenase 2 Endothelium Endothelium, Vascular - cytology Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Enzyme Inhibitors - pharmacology Female Fetal Hemoglobin - metabolism Hematology Hemodynamics Hemoglobin Hemoglobin, Sickle - genetics Hemoglobin, Sickle - metabolism Hemolysis - physiology Humans Inflammation Isoenzymes - metabolism Male Membrane Proteins Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Microcirculation - metabolism Muscle, Skeletal - cytology Muscle, Skeletal - metabolism NG-Nitroarginine Methyl Ester - pharmacology Nitric Oxide - metabolism Nitric Oxide Synthase - metabolism Nitric Oxide Synthase Type II Nitric Oxide Synthase Type III Nitroprusside - pharmacology Oxidative Stress Prostaglandin-Endoperoxide Synthases - metabolism Regulation Sickle cell disease Tyrosine - analogs & derivatives Tyrosine - metabolism Vasodilation - physiology Vasodilator Agents - pharmacology
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Zusammenfassung:	In sickle cell disease, intravascular sickling and attendant flow abnormalities underlie the chronic inflammation and vascular endothelial abnormalities. However, the relationship between sickling and vascular tone is not well understood. We hypothesized that sickling-induced vaso-occlusive events and attendant oxidative stress will affect microvascular regulatory mechanisms. In the present studies, we have examined whether microvascular abnormalities expressed in sickle transgenic-knockout Berkeley (BERK) mice (which express exclusively human alpha- and beta(S)-globins with
ISSN:	0021-9738 1558-8238
DOI:	10.1172/JCI200421633